Cymbalta In The News...Again (Part 1)

Does your medication contain the NDMA contaminant?

The commonly used antidepressant, duloxetine, sold in the US by the trade name Cymbalta, continues to make headlines due to elevated levels of N-nitroso-duloxetine (NDLX) in numerous bottles on routine testing. The amount of N-nitroso-duloxetine was found to be above the proposed limit (600 ng/day); the recommended acceptable intake limit is 100 ng/day.

• On Oct. 10, 2024, FDA issued a recall of 7,100 bottles of 20 mg delayed-release capsules (500-count bottles.) manufactured by Towa Pharmaceutical Europe. The recalled batch, lot number 220128, has an expiration date of December 2024.

• On Nov. 19, Rising Pharmaceuticals, Inc. voluntarily recalled 233,003 bottles of various doses of duloxetine delayed-release Cymbalta capsules due to the presence of N-nitroso-duloxetine impurity above the recommended limit.

• On December 5, the recalled drugs were given a Class II risk level designation, the second-most extreme risk issued by the FDA for a drug or medical device. This concern was explained this way by David Cosio, PhD, ABPP from Brown University VA Medical Center in Chicago:

“The chemicals found in duloxetine put patients at a higher risk of developing cancer when they are present in higher concentrations and when patients are exposed to them for an extended period of time.”

What is Duloxetine?

Duloxetine, the active ingredient in and commonly known as Cymbalta, is widely prescribed to treat anxiety and depression in adults and children as young as 7 years of age. In the US, the medication grossed billions in sales for its manufacturer, Eli Lilly. It is often prescribed in an off-label format to treat fibromyalgia, peripheral neuropathy, and osteoarthritis. It works by increasing the amounts of serotonin and norepinephrine in the brain. Before the patent expired in 2012, Cymbalta generated $4.99 billion globally, reflecting a 20% increase from the prior year, with $3.92 billion coming from U.S. sales. By 2013, annual revenue still reached approximately $5 billion.

What are the Side Effects and Precautions for using Cymbalta

There are many concerns with taking this drug. Here are a few (not all-inclusive) problems that were found:

When prescribing Cymbalta, use caution:

• In patients with a history of mania, bipolar disorder, or seizures.

• In patients with increased intraocular pressure or acute narrow-angle glaucoma.

• In patients with high blood pressure and other cardiac diseases, including arrhythmias.

• In patients with severe renal impairment.

• In patients with elevated liver enzymes.

• Long-lasting sexual dysfunction has continued despite discontinuation.

• In patients with bleeding abnormalities, including gastrointestinal hemorrhage and postpartum hemorrhage,

• In patients taking anticoagulants, NSAIDs, or aspirin.

It has been associated with an increased risk of self-harm and suicide-related events. Suicide-related behaviors (suicide attempts and suicidal thoughts) and hostility (predominantly aggression, oppositional behavior, and anger) were more frequently observed in children and teenagers.

Excipients in Cymbalta

Nitrosamine impurities can form during the manufacture or storage of the drugs. The compounds may arise through chemical reactions involving the formulation's active pharmaceutical ingredient (API) or with the drug’s excipients. Factors such as high temperatures, pH fluctuations, or the presence of nitrites during production or storage can accelerate their formation.

Similar to how we frequently think about vaccines – that they contain a little “killed” or attenuated virus – we think that prescription medications only contain the active ingredient and a coating. Both ideas are false. Take a look at the extra, added ingredients in Cymbalta:

Capsule content:

• Sugar spheres - contain maize starch and sucrose

• Hypromellose 2910 (E464)- a binder, film-forming agent, and controlled-release agent

• Crospovidone (type B) - synthetic polymer commonly used to assist in the disintegration of tablets in the digestive tract to release the active ingredient.

• Talc – flow agent

• Carboxy-methyl ethyl cellulose - thickening agent, binder, and disintegrant in pharmaceutical formulations, particularly in tablets, capsules, and suspensions.

• Povidone - a binder in tablet formulations, a disintegrant, and sometimes as a stabilizer for active ingredients. It helps improve the solubility.

• Titanium dioxide (E171) - a binder and coating agent

• Macrogol (E1521) - polyethylene glycol

• Polysorbate 80 (E433)

• Sucrose

Capsule shell:

• Sodium lauryl sulfate - acts as a surfactant, reducing the surface tension between the tablet ingredients.

• Iron oxide yellow (E172) – coloring agent

• Indigo carmine (E132) - petrochemical derivative that is a synthetic colorant

• Gelatin

• Titanium dioxide (E171)

Edible ink:

• Shellac (E904)

• Propylene glycol

• Black iron oxide (E172) – coloring agent

• Potassium hydroxide

If you want to stop taking Cymbalta or any of your other prescription medications, do not stop them abruptly without consulting your doctor or at least a local pharmacist. Many can be simply eliminated, but some must be weaned out of your body slowly to avoid side effects or rebound effects, which can be severe, even deadly. Adverse events seen on abrupt treatment discontinuation of Cymbalta occurred in approximately 44% of patients.

Almost all medicines, including over-the-counter medications, can be thrown into your household trash. The FDA recommends the following steps:

1. Remove the drugs from their original containers and mix them with something undesirable, such as used coffee grounds, dirt, or cat litter. This makes the medicine less appealing to children and pets, and unrecognizable to someone who might intentionally go through the trash looking for drugs.

2. To prevent the drug from leaking or spilling out, put the mixture in a zip-lock storage bag, an empty can, a jar with a lid, or another container.

3. Throw the container in the garbage.

4. Scratch out all your personal information on the empty medicine packaging to protect your identity and privacy.

5. Throw the plastic bottles in the recycling bin.